Journal Article

Nutritional combinatorial impact on the gut microbiota and plasma short-chain fatty acids levels in the prevention of mammary cancer in Her2/neu estrogen receptor-negative transgenic mice

Sharma, Manvi, Li, Shizhao, Li, Yuanyuan, Tollefsbol, Trygve O., Berryhill, Taylor F., Barnes, Stephen, Arora, Itika, Stoll, Matthew L., Morrow, Casey D.

2020

Overview

Breast cancer is the second leading cause of cancer-related mortality in women. Various nutritional compounds possess anti-carcinogenic properties which may be mediated through their effects on the gut microbiota and its production of short-chain fatty acids (SCFAs) for the prevention of breast cancer. We evaluated the impact of broccoli sprouts (BSp), green tea polyphenols (GTPs) and their combination on the gut microbiota and SCFAs metabolism from the microbiota in Her2/neu transgenic mice that spontaneously develop estrogen receptor-negative [ER(-)] mammary tumors. The mice were grouped based on the dietary treatment: control, BSp, GTPs or their combination from beginning in early life (BE) or life-long from conception (LC). We found that the combination group showed the strongest inhibiting effect on tumor growth volume and a significant increase in tumor latency. BSp treatment was integrally more efficacious than the GTPs group when compared to the control group. There was similar clustering of microbiota of BSp-fed mice with combination-fed mice, and GTPs-fed mice with control-fed mice at pre-tumor in the BE group and at pre-tumor and post-tumor in the LC group. The mice on all dietary treatment groups incurred a significant increase of Adlercreutzia , Lactobacillus genus and Lachnospiraceae, S24-7 family in the both BE and LC groups. We found no change in SCFAs levels in the plasma of BSp-fed, GTPs-fed and combination-fed mice of the BE group. Marked changes were observed in the mice of the LC group consisting of significant increases in propionate and isobutyrate in GTPs-fed and combination-fed mice. These studies indicate that nutrients such as BSp and GTPs differentially affect the gut microbial composition in both the BE and LC groups and the key metabolites (SCFAs) levels in the LC group. The findings also suggest that temporal factors related to different time windows of consumption during the life-span can have a promising influence on the gut microbial composition, SCFAs profiles and ER(-) breast cancer prevention.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Actinobacteria - drug effects / Actinobacteria - isolation & purification / Actinobacteria - physiology / Animals / Apoptosis / Biology / Biology and Life Sciences / Brassica - chemistry / Breast cancer / Broccoli / Cancer therapies / Carcinogens / Cell cycle / Clostridiales - drug effects / Clostridiales - isolation & purification / Clostridiales - physiology / Clustering / Combinatorial analysis / Composition / Diet / Diet - methods / Disease prevention / Enzymes / Epigenetics / ErbB-2 protein / Estrogen receptors / Estrogens / Fatty acids / Fatty Acids, Volatile - blood / Female / Gastrointestinal Microbiome - drug effects / Gastrointestinal Microbiome - physiology / Gene Expression / Green tea / Gut microbiota / Health aspects / Intestinal microflora / Kinases / Laboratories / Lactobacillus - drug effects / Lactobacillus - isolation & purification / Lactobacillus - physiology / Latency / Mammary Glands, Animal - drug effects / Mammary Glands, Animal - metabolism / Mammary Glands, Animal - pathology / Mammary Neoplasms, Experimental - blood / Mammary Neoplasms, Experimental - genetics / Mammary Neoplasms, Experimental - pathology / Mammary Neoplasms, Experimental - prevention & control / Medical nutrition therapy / Medicine and Health Sciences / Metabolism / Metabolites / Methods / Mice / Mice, Knockout / Microbiota / Microbiota (Symbiotic organisms) / Microorganisms / Nutrients / Polyphenols / Polyphenols - chemistry / Polyphenols - pharmacology / Prevention / Propionic acid / Proteomics / Receptor, ErbB-2 - deficiency / Receptor, ErbB-2 - genetics / Receptors / Receptors, Estrogen - deficiency / Receptors, Estrogen - genetics / Research and Analysis Methods / Seedlings - chemistry / Tea / Tea - chemistry / Transgenic mice / Tumors / Vegetables / Windows (intervals) / Womens health